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Abstract：
X-linked adrenoleukodystrophy (X-ALD) is a severe inherited metabolic disease with cerebral inflammatory demyelination and abnormal accumulation of very long chain fatty acid (VLCFA) in tissues, especially the brain. At present, bone marrow transplantation (BMT) at an early stage of the disease is the only effective treatment for halting disease progression, but the underlying mechanism of the treatment has remained unclear. Here, we transplanted GFP-expressing wild-type (WT) or Abcd1-deficient (KO) bone marrow cells into recipient KO mice, which enabled tracking of the donor GFP+ cells in the recipient mice. Both the WT and KO donor cells were equally distributed throughout the brain parenchyma, and displayed an Iba1-positive, GFAP- and Olig2-negative phenotype, indicating that most of the donor cells were engrafted as microglia-like cells. They constituted approximately 40% of the Iba1-positive cells. Unexpectedly, no decrease of VLCFA in the cerebrum was observed when WT bone marrow cells were transplanted into KO mice. Taken together, murine study suggests that bone marrow-derived microglia-like cells engrafted in the cerebrum of X-ALD patients suppress disease progression without evidently reducing the amount of VLCFA in the cerebrum.
摘要：
X-连锁肾上腺脑白质营养不良（X-ALD）是一种严重的遗传性代谢疾病，具有脑炎症性脱髓鞘和组织中超长链脂肪酸（VLCFA）的异常积累，尤其是大脑。目前,在疾病的早期阶段进行骨髓移植（BMT）是阻止疾病进展的唯一有效治疗方法，但治疗的潜在机制仍不清楚.这里,我们将表达GFP的野生型（WT）或Abcd1缺陷（KO）骨髓细胞移植到受体KO小鼠中，这使得能够在受体小鼠中追踪供体GFP+细胞。WT和KO供体细胞在整个脑实质中均匀分布，显示Iba1阳性，GFAP和Olig2阴性表型，表明大多数供体细胞被移植为小胶质细胞样细胞。它们构成Iba1阳性细胞的大约40%。出乎意料的是,将WT骨髓细胞移植到KO小鼠中时，未观察到大脑中VLCFA的减少。一起来看,鼠研究表明，移植到X-ALD患者大脑中的骨髓来源的小胶质细胞样细胞可抑制疾病进展，而不会显着减少大脑中VLCFA的含量。
